Investigation continues to determine if modest hypothermia (reduction in temperature of only 2-3 oC) provides neuroprotection for neonatal brain ischemia. Previous studies have demonstrated that modest hypothermia is neuro-protective when employed during a 15 min interval of partial brain ischemia or in the first 60 min immediately following ischemia. The investigation conducted this past year was designed to determine if modest hypothermia provides neuro-protection when initiated 30 min following partial brain ischemia. This experi-mental design addresses whether a therapeutic window exists, which would allow neuroprotective strategies to be initiated at an interval following ischemia. All experiments were conducted in neonatal swine during the first two weeks of life. Eleven animals were maintained normothermic (rectal temperature 38-38.5 oC) before, during 15 min of partial brain ischemia, and for 120 min following ischemia. Eleven animals were handled in an identical fashion except that rectal temperature was reduced to 35.5-36oC for a 60 min interval commencing at 30 min following ischemia. Preliminary data confirmed differences in rectal temperature between groups resulted in similar differences in brain temperature. All animals were recovered for 72 hours following ischemia during which time a daily neurobehavioral score was performed. At study completion, brain perfusion/ fixation was used for histologic assessment of 16 different brain regions. 31P MRS verified that the severity of ischemia was similar between groups. There were also no differences between groups in any systemic variable measured (arterial blood pressure, pH, blood gases, glucose and lactate concentration). The important results of this investigation were: 1) no differences between groups in the extent of encephalopathy following ischemia and 2) no differences between groups in the extent of neuronal damage in any brain region. The results demonstrate that a short interval (60 min) of modest hypothermia initiated 30 min following ischemia does not provide neuroprotection. The presence of a therapeutic window is not supported by this investigation; the results however do not exclude a therapeutic window being evident if a longer interval of modest hypothermia is employed post-ischemia.